CDK4/6 Inhibitor Palbociclib Amplifies the Radiosensitivity to Nasopharyngeal Carcinoma Cells via Mediating Apoptosis and Suppressing DNA Damage Repair

CDK4/6 Inhibitor Palbociclib Amplifies the Radiosensitivity to Nasopharyngeal Carcinoma Cells via Mediating Apoptosis and Suppressing DNA Damage Repair:

Authors Xie X, Zheng W, Chen T, Lin W, Liao Z, Liu J, Ding Y



Received 10 October 2019



Accepted for publication 26 November 2019



Published 16 December 2019 Volume 2019:12 Pages 11107—11117



DOI https://doi.org/10.2147/OTT.S234221



Checked for plagiarism Yes



Review by Single-blind



Peer reviewers approved by Ms Swati Sharma



Peer reviewer comments 2



Editor who approved publication: Dr Gaetano Romano





Xianhe Xie,1,* Weili Zheng,1,2,* Ting Chen,1,2 Wanzun Lin,1,2 Ziyuan Liao,1 Junjin Liu,1 Yin Ding1



1Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, People’s Republic of China; 2Department of Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, People’s Republic of China



*These authors contributed equally to this work



Correspondence: Xianhe Xie

Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, 20th Chazhong Road, Fuzhou 350005, Fujian, People’s Republic of China

Tel +86 183 0591 5132

Fax +86 591 8798 1028

Email xiexianhe@fjmu.edu.cn



Background: Radiotherapy is the primary approach for nasopharyngeal carcinoma (NPC). Although high survival rates can be obtained with radiation for early stage lesions, distant metastasis and local recurrence frequently occur. In this study, we pioneeringly investigated the antitumor activity and underlying mechanism of cyclin-dependent kinase 4/6 inhibitor (palbociclib) combined with radiation on NPC cells.

Methods: Evaluation of radiation enhancement with palbociclib was based on results from CCK8 and clonogenicity assays for cell proliferation, flow cytometry for apoptosis, ROS level and cell cycle and immunocytochemistry for DNA double-strand break repair.

Results: Palbociclib inhibited cellular growth of RB-proficient CNE-1 and CNE-2 via reducing RB phosphorylation and arresting cell cycle. Combination regimens of palbociclib plus radiation were significantly superior to palbociclib or radiation only through inhibiting cellular growth and inducing apoptosis. Moreover, the antitumor activity of both concurrent palbociclib plus radiation and radiation followed by palbociclib consistently preceded that of palbociclib followed by radiation. Meanwhile, the two preferable combination regimens possessed higher proportion of G2/M phase cells, evidently inhibited DNA double-strand break repair and eventually triggered tumor cell apoptosis.

Conclusion: Our study demonstrated that palbociclib could provoke a strong antitumor activity as a potential adjuvant to radiation therapy for NPC harboring RB expression.



Keywords: nasopharyngeal carcinoma, palbociclib, radiotherapy, apoptosis, DNA damage repair